Are Anesthesia and Surgery during Infancy Associated with Decreased White Matter Integrity and Volume during Childhood?

BACKGROUND: Anesthetics have neurotoxic effects in neonatal animals. Relevant human evidence is limited. We sought such evidence in a structural neuroimaging study. METHODS: Two groups of children underwent structural magnetic resonance imaging: patients who, during infancy, had one of four operations commonly performed in otherwise healthy children and comparable, nonexposed control subjects. Total and regional brain tissue composition and volume, as well as regional indicators of white matter integrity (fractional anisotropy and mean diffusivity), were analyzed. RESULTS: Analyses included 17 patients, without potential confounding central nervous system problems or risk factors, who had general anesthesia and surgery during infancy and 17 control subjects (age ranges, 12.3 to 15.2 yr and 12.6 to 15.1 yr, respectively). Whole brain white matter volume, as a percentage of total intracranial volume, was lower for the exposed than the nonexposed group, 37.3 ± 0.4% and 38.9 ± 0.4% (least squares mean ± SE), respectively, a difference of 1.5 percentage points (95% CI, 0.3 to 2.8; P = 0.016). Corresponding decreases were statistically significant for parietal and occipital lobes, infratentorium, and brainstem separately. White matter integrity was lower for the exposed than the nonexposed group in superior cerebellar peduncle, cerebral peduncle, external capsule, cingulum (cingulate gyrus), and fornix (cres) and/or stria terminalis. The groups did not differ in total intracranial, gray matter, and cerebrospinal fluid volumes. CONCLUSIONS: Children who had anesthesia and surgery during infancy showed broadly distributed, decreased white matter integrity and volume. Although the findings may be related to anesthesia and surgery during infancy, other explanations are possible.

Anesthesia and the developing brain.

Despite the profound evolution in the safety and efficacy of neonatal and pediatric anesthesia, questions remain concerning the long-term neurotoxic and neurocognitive effects of the drugs used in anesthetic care. A variety of prospective animal models and retrospective human studies exist that inconsistently demonstrate a detrimental effect of early life exposure to anesthetic drugs and subsequent learning performance. Limitations associated with both non-human and human observational studies are critiqued. Research currently underway is briefly described. A framework for discussing the relevant issues with concerned parents is presented.

Tentative evidence for striatal hyperactivity in adolescent cannabis-using boys: a cross-sectional multicenter fMRI study.

Adolescents' risk-taking behavior has been linked to a maturational imbalance between reward ("go") and inhibitory-control ("stop")-related brain circuitry. This may drive adolescent drug-taking, such as cannabis use. In this study, we assessed the non-acute effects of adolescent cannabis use on reward-related brain function. We performed a two-site (United States and Netherlands; pooled data) functional magnetic resonance imaging (fMRI) study with a cross-sectional design. Twenty-one abstinent but frequent cannabis-using boys were compared with 24 non-using peers on reward-related brain function, using a monetary incentive delay task with fMRI. Focus was on anticipatory and response stages of reward and brain areas critically involved in reward processing like the striatum. Performance in users was normal. Region-of-interest analysis indicated striatal hyperactivity during anticipatory stages of reward in users. Intriguingly, this effect was most pronounced during non-rewarding events. Striatal hyperactivity in adolescent cannabis users may signify an overly sensitive motivational brain circuitry. Frequent cannabis use during adolescence may induce diminished ability to disengage the motivational circuit when no reward can be obtained. This could strengthen the search for reinforcements like drugs of abuse, even when facing the negative (non-rewarding) consequences.

Are anesthesia and surgery during infancy associated with altered academic performance during childhood?

BACKGROUND: Although studies in neonatal animals show that anesthetics have neurotoxic effects, relevant human evidence is limited. We examined whether children who had surgery during infancy showed deficits in academic achievement. METHODS: We attempted to contact parents of 577 children who, during infancy, had one of three operations typically performed in otherwise healthy children. We compared scores on academic achievement tests with population norms. RESULTS: Composite scores were available for 287 patients. The mean normal curve equivalent score was 43.0±22.4 (mean±SD), lower than the expected normative value of 50, P<0.0001 by one-sample Student t test; and 35 (12%) had scores below the 5th percentile, more than expected, P<0.00001 by binomial test. Of 133 patients who consented to participate so that their scores could be examined in relation to their medical records, the mean score was 45.9±22.9, P=0.0411; and 15 (11%) scored below the 5th percentile, P=0.0039. Of 58 patients whose medical records showed no central nervous system problems/potential risk factors during infancy, 8 (14%) scored below the 5th percentile, P=0.008; however, the mean score, 47.6±23.4, was not significantly lower than expected, P=0.441. Duration of anesthesia and surgery correlated negatively with scores (r=-0.34, N=58, P=0.0101). CONCLUSIONS: Although the findings are consistent with possible adverse effects of anesthesia and surgery during infancy on subsequent academic achievement, other explanations are possible and further investigations are needed.

Clinical, methodological and theoretical issues in the assessment of cognition after anaesthesia and surgery: a review.

As people live longer, the burden of cognitive impairment to elderly patients, their families and society becomes increasingly common and important. The loss of independence, a reduction in the quality of life and increased mortality are possible correlates to the mental disintegration. Cognitive dysfunction following major surgery on the elderly is a significant problem which adds to other cognitive impairments caused by neurodegeneration, cerebrovascular impairments and other causes. There are challenges in reviewing the literature because of many methodological concerns. There is no standard definition; the diagnosis is made only by the results of neuropsychological tests which are not standardised for this purpose; test results are analysed by different statistical methods (some of them inappropriate); controls are often absent or poorly matched; and pre-existing mild cognitive impairment, which affects 10 to 20% of people older than 65 years and is similar to the subtle cognitive impairment following surgery, is not sought for and recognised. Reviews of the subject have varied from descriptions such as 'a well recognised and significant problem' to 'a hypothetical phenomenon for which there is no International Statistical Classification of Disease (ICD-9) code, and no Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) code'. This article examines both sides of the spectrum in a detailed review which explains the necessary psychological 'jargon', discusses the methods used and points to areas of future research.

Associations of Regular Marijuana Use by Adolescent Boys With Verbal Memory and Perseveration.

Many American and Dutch adolescents use marijuana regularly. There is concern that such use may impair cognitive function more in adolescents than adults. We examined effects of regular marijuana use on long-term memory and perseveration among American and Dutch adolescents. We administered Buschke's Selective Reminding Test (BSRT) to assess long-term memory and the Wisconsin Card Sorting Test (WCST) to assess perseveration in male teenagers. Usable test data were obtained for 12 American marijuana users, 13 American controls, 9 Dutch marijuana users, and 12 Dutch controls. In BSRT, users showed lower overall long-term storage than controls (adjusted means ± SE's for numbers of words per trial of 9.4 ± 0.2, 13.4 ± 0.3, 11.7 ± 0.2, and 12.4 ± 0.2 for American users, Dutch users, American controls, and Dutch controls, respectively). Marijuana was associated with memory effects only in American, not Dutch, users. Bivariate Pearson correlations for American and Dutch users combined showed associations of lower total recall with more uses in the previous year and lifetime (r = -0.61 and r = -0.53, respectively); and more perseverative errors with more uses in the previous year (r = 0.55). Some findings were consistent with the possibility that regular adolescent marijuana use causes deficits in cognition, especially memory. However, a causal interpretation cannot be inferred from our findings and is challenging to reconcile with the observation of memory deficits only in American users. Our study was novel in examining the influence of nationality on marijuana's cognitive effects. More studies of this topic should compare effects across nationalities or cultures.

Sex differences in the effects of marijuana on simulated driving performance.

In the United States, one in six teenagers has driven under the influence of marijuana. Driving under the influence of marijuana and alcohol is equally prevalent, despite the fact that marijuana use is less common than alcohol use. Much of the research examining the effects of marijuana on driving performance was conducted in the 1970s and led to equivocal findings. During that time, few studies included women and driving simulators were rudimentary. Further, the potency of marijuana commonly used recreationally has increased. This study examined sex differences in the acute effects of marijuana on driving performance using a realistic, validated driving simulator. Eighty-five subjects (n = 50 males, 35 females) participated in this between-subjects, double-blind, placebo controlled study. In addition to an uneventful, baseline segment of driving, participants were challenged with collision avoidance and distracted driving scenarios. Under the influence of marijuana, participants decreased their speed and failed to show expected practice effects during a distracted drive. No differences were found during the baseline driving segment or collision avoidance scenarios. No differences attributable to sex were observed. This study enhances the current literature by identifying distracted driving and the integration of prior experience as particularly problematic under the influence of marijuana.

Sex, drugs, and cognition: effects of marijuana.

Despite the knowledge that many drugs affect men and women differently, few studies exploring the effects of marijuana use on cognition have included women. Findings from both animal and human studies suggest marijuana may have more marked effects in women. This study examined sex differences in the acute effects of marijuana on cognition in 70 (n=35 male, 35 female) occasional users of marijuana. Tasks were chosen to tap a wide variety of cognitive domains affected by sex and/or marijuana including attention, cognitive flexibility, time estimation, and visuospatial processing. As expected, acute marijuana use impaired performance on selective and divided attention, time estimation, and cognitive flexibility. While there did not appear to be sex differences in marijuana's effects on cognition, women requested to discontinue the smoking session more often than men, likely leading to an underestimation of differences. Further study of psychological differences in marijuana's effects on men and women following both acute and residual effects of marijuana is warranted.

Do Departments in a College of Medicine Differ in Academic Productivity As Assessed by the H-Indices of Tenured Faculty Members?

BACKGROUND: It is uncertain how different academic medical departments differ in academic productivity as assessed by commonly used bibliometric measures, eg, the h-index (the maximum value of h such that an author has published h papers that have each been cited at least h times). AIM: This project examined whether departments in the University of Iowa's Carver College of Medicine differed in h-indices of tenured faculty members. METHODS: Based on 2020 data obtained from the College (and other University sources), the author compiled three data sets of Scopus h-indices of tenured faculty members identified by department, varying in size due to slightly different inclusion criteria (N's=334, 341, and 354). Analyses compared h-indices between ranks and among departments. RESULTS: In the basic data set (N=334), h-indices of the 230 (69%) full and 104 (31%) associate professors differed based on a t-test, means (standard deviations)=37 (17) and 20 (7), respectively, p<0.0001. For both full and associate professors separately, departments differed in h-indices based on analyses of variance, p=0.04 and p=0.02, respectively. In the expanded data sets, departmental differences were significant for full and associate professors (with N=341) and full professors (with N=354). CONCLUSION: Departments differed in academic productivity of tenured faculty members as assessed by h-indices. This was not a powerful, monolithic effect, ie, relative departmental standings for full and associate professors were not consistent, and departmental differences for associate professors were nonsignificant in the largest (N=354) data set. Multiple factors probably contributed to departmental differences and should be further investigated.

Is Exhaustion More Sensitive Than Disengagement to Burnout in Academic Anesthesia? A Study Using the Oldenburg Burnout Inventory.

Reportedly, clinicians of all kinds are experiencing alarming rates of burnout, and its prevalence among anesthesia providers is high. We examined burnout in a large academic anesthesia department with a commonly used questionnaire, the Oldenburg Burnout Inventory, which provides scores on two scales, "exhaustion" and "disengagement." We examined differences in scores between exhaustion and disengagement and their prevalences. All N = 415 staff members of the department were requested to complete the Oldenburg Burnout Inventory and N = 130 (31%) did so. The mean ± standard deviation was 2.52 ± 0.51 (range, 1.13 to 3.75) for exhaustion and 2.27 ± 0.52 (range, 1.13 to 3.63) for disengagement. The mean for exhaustion exceeded that for disengagement by 0.25 ± 0.42 (range, -1.25 to 1.25), t(129)=6.68, p < 0.0001 by paired t test. Mean ratings exceeded the midpoint (2.5) between the "burned out" and "not burned out" ends of the rating scale for 49% of respondents for exhaustion, but only 30% for disengagement. More respondents (N = 87, 67%) had a higher mean for exhaustion than disengagement than the opposite pattern (N = 28, 22%), M = 29.5, p < 0.0001 by sign test. Thus, burnout symptoms were common but reflected more in exhaustion than disengagement. Literature review suggested that the difference between the exhaustion and disengagement means that we found was larger than typical, but not unusual, for health-care-related groups, and typical for other groups. Future studies should clarify circumstances under which exhaustion exceeds disengagement and vice versa, both in anesthesia and other fields.

Awareness during anesthesia: risk factors, causes and sequelae: a review of reported cases in the literature.

BACKGROUND: Awareness during anesthesia is uncommon. The number of cases that are found in one single study are insufficient to identify and estimate the risks, causal factors and sequelae. One method of studying a large number of cases is to analyze reports of cases of awareness that have been published in scientific journals. METHODS: We conducted an electronic search of the literature in the National Library of Medicine's PubMed database for case reports on "Awareness" and "Anesthesia" for the time period between 1950 through August, 2005. We also manually searched references cited in these reports and in other articles on awareness. We used two surgical control groups for comparative purposes. The first group in a study by Sebel et al. consisted of patients who did not experience awareness. The second group, from the 1996 data from the National Survey of Ambulatory Surgery included patients who received general anesthesia. We also used data from the National Center for Health Statistics to compare weight and Body Mass Index. RESULTS: We compared the data of 271 cases of awareness with 19,504 patients who did not suffer it. Aware patients were more likely to be females (P < 0.05), younger (P < 0.001) and to have cardiac and obstetrics operations (P < 0.0001). Only 35% reported the awareness episode during the stay in the recovery room. They received fewer anesthetic drugs (P < 0.0001), and were more likely to exhibit episodes of tachycardia and hypertension during surgery (P < 0.0001). A much larger percentage of these patients (52%, P < 0.0001) voiced postoperative complaints related to awareness. Inability to move and feelings such as helplessness, sensation of weakness, and hearing noises and voices were related to the persistence of complaints such as sleep disturbances and fear about future anesthetics (P < 0.041-0.0003). Twenty-two percent of the patients suffered late psychological symptoms. CONCLUSIONS: Our review suggested light anesthesia and a history of awareness as risk factors. Obesity and avoidance of nitrous oxide use did not seem to increase the risk. Light anesthesia was the most common cause. Our findings suggest preventive procedures that may lead to a decrease in the incidence of awareness.

Iowa Case Management for Rural Drug Abuse.

OBJECTIVE: The purpose of this research was to evaluate the effectiveness of a comprehensive, strengths-based model of case management for clients in drug abuse treatment. METHOD: 503 volunteers from residential or intensive outpatient treatment were randomly assigned to one of three conditions of Iowa Case Management (ICM) plus treatment as usual (TAU), or to a fourth condition of TAU only. All were assessed at intake and followed at 3, 6, and 12 months. RESULTS: Clients in all four conditions significantly decreased substance use by 3 months after intake and maintained most gains over time. However, the addition of ICM to TAU did not improve substance use outcomes. CONCLUSION: Overall, the addition of case management did not significantly improve drug treatment as hypothesized by both researchers and clinicians. Some results were mixed, possibly due to the heterogeneous sample, wide range of case management activities, or difficulty retaining participants over time.

The Relationship of Exposure to Anesthesia on Outcomes in Children With Isolated Oral Clefts.

This study evaluated the relationship between exposure to anesthesia and previously identified differences in cognitive functioning, growth, and volumetric brain measures among a sample of children, adolescents, and young adults with isolated oral clefts. Data from a cross-sectional study were combined with a retrospective chart review. Data were obtained for 87 participants with isolated cleft lip and/or palate (55% male), ranging from 7.5 to 27 years old (mean = 15.78, standard deviation = 4.58). Measures of interest included cognitive functioning, growth measures, and brain volumes. Number of surgeries and time under anesthesia were obtained through systematic medical record review. Potential sex and cleft type differences in exposure as well as relationships between anesthesia exposure and outcome measures were evaluated. Participants with isolated cleft lip and palate had more surgeries and were under anesthesia longer. For participants with isolated cleft lip only, more surgeries were correlated to lower verbal IQ and higher frontal lobe volume.

Methods for studying acute and chronic effects of marijuana on human associative processes and memory.

This chapter summarizes the methods and results of studies in which the author examined the acute or chronic effects of marijuana on human associative processes and memory. Eleven tests used to assess marijuana's effects on associative processes, semantic memory, and episodic memory are described.

Effects of smoking marijuana on brain perfusion and cognition.

The effects of smoking marijuana on regional cerebral blood flow (rCBF) and cognitive performance were assessed in 12 recreational users in a double-blinded, placebo-controlled study. PET with [(15)Oxygen]-labeled water ([(15)O]H(2)O) was used to measure rCBF before and after smoking of marijuana and placebo cigarettes, as subjects repeatedly performed an auditory attention task. Smoking marijuana resulted in intoxication, as assessed by a behavioral rating scale, but did not significantly alter mean behavioral performance on the attention task. Heart rate and blood pressure increased dramatically following smoking of marijuana but not placebo cigarettes. However, mean global CBF did not change significantly. Increased rCBF was observed in orbital and mesial frontal lobes, insula, temporal poles, anterior cingulate, as well as in the cerebellum. The increases in rCBF in anterior brain regions were predominantly in "paralimbic" regions and may be related to marijuana's mood-related effects. Reduced rCBF was observed in temporal lobe auditory regions, in visual cortex, and in brain regions that may be part of an attentional network (parietal lobe, frontal lobe and thalamus). These rCBF decreases may be the neural basis of perceptual and cognitive alterations that occur with acute marijuana intoxication. There was no significant rCBF change in the nucleus accumbens or other reward-related brain regions, nor in basal ganglia or hippocampus, which have a high density of cannabinoid receptors.

Marijuana alters the human cerebellar clock.

The effects of marijuana on brain perfusion and internal timing were assessed using [15O] water PET in occasional and chronic users. Twelve volunteers who smoked marijuana recreationally about once weekly, and 12 volunteers who smoked daily for a number of years performed a self-paced counting task during PET imaging, before and after smoking marijuana and placebo cigarettes. Smoking marijuana increased rCBF in the ventral forebrain and cerebellar cortex in both groups, but resulted in significantly less frontal lobe activation in chronic users. Counting rate increased after smoking marijuana in both groups, as did a behavioral measure of self-paced tapping, and both increases correlated with rCBF in the cerebellum. Smoking marijuana appears to accelerate a cerebellar clock altering self-paced behaviors.

Effect of acute marijuana on cardiovascular function and central nervous system pharmacokinetics of [(15)O]water: effect in occasional and chronic users.

The objective of this study was to evaluate the effect of the acute administration of marijuana (MJ) on cardiovascular (CV) function and CNS pharmacokinetics (PK) of [(15)O]water in occasional (O) versus chronic (C) MJ users. Each subject received four injections of [(15)O]water (one prior and three postsmoking) on two occasions in which they received active or placebo MJ. For each injection, measures of CV function and CNS PK [(15)O]water were made. Postsmoking, MJ influenced all measured CV and [(15)O]water PK parameters. C users reported significantly lower "highness" and smaller heart rate (HR) changes, which resulted in reduced rate pressure product (RPP) changes compared to O users, even though Delta(9)-tetrahydrocannabinol levels were higher, whereas changes in blood pressure (BP), arrival time, and [(15)O]water concentration were not significantly different between the groups. Significant CV changes resulted in changes in the whole-body distribution of cardiac output rather than changes in cerebral blood flow. Chronic MJ use produces tolerance to the HR increases induced by acute MJ smoking compared to changes observed in occasional users, without changing the effects on BP and [(15)O]water PK.